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This has enabled the replacement of the designated thorough QT (TQT) study with serial electrocardiograms (ECGs) in routine clinical pharmacology studies, such as the first\u2010in\u2010human (FIH) study. The E14 revision\u00a0has led to an increased proportion of FIH studies with the added objective of QT evaluation, with the intention of replacing the TQT study. With the more recent revision of the S7B\/E14 Q&amp;A document in February 2022, nonclinical assays\/studies can be brought into the process of regulatory decisions at the time of marketing application. If the hERG (human ether\u2010a\u2010go\u2010go\u2010related gene) and the non\u2010rodent in\u00a0vivo study are conducted according to the described best practices and are negative, the previous requirement that a QTc effect of &gt;10\u00a0milliseconds must be excluded in healthy subjects at plasma concentrations 2\u2010fold above what can be seen in patients can be reduced to covering the concentrations seen in patients. For drugs that cannot be safely given in high doses to healthy subjects, ECG evaluation is often performed at the therapeutic dose in patients. If a QTc effect of &gt;10\u00a0milliseconds can be excluded, an argument can be made that the drug should be considered as having a low likelihood of proarrhythmic effects due to delayedrepolarization, if supported by negative best practices hERG and in vivo studies. In this article, we describe what clinicians involved in early clinical development need to understand in terms of the hERG and in\u00a0vivo studies to determine whether these meet best practices and therefore can be used in an integrated clinical\/nonclinical QT\/QTc risk assessment.<\/jats:p>","DOI":"10.1002\/jcph.2309","type":"journal-article","created":{"date-parts":[[2023,7,17]],"date-time":"2023-07-17T05:34:22Z","timestamp":1689572062000},"page":"1256-1274","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The New S7B\/E14 Q&amp;A Document Provides Additional Opportunities to Replace the Thorough QT Study"],"prefix":"10.1002","volume":"63","author":[{"given":"Borje","family":"Darpo","sequence":"first","affiliation":[{"name":"Clario Rochester NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek J.","family":"Leishman","sequence":"additional","affiliation":[{"name":"Eli Lilly and Company Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,8,2]]},"reference":[{"key":"e_1_2_12_2_1","unstructured":"ICH.S7B\/E14 Q&A: Clinical and Nonclinical Evaluation of QT\/QTc Interval Prolongation and Proarrhythmic Potential. 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